Archive for category tDCS/rTMS

Abstract

Objective. Combining repetitive transcranial magnetic stimulation (rTMS) with brain-computer interface (BCI) training can address motor impairment after stroke by down-regulating exaggerated inhibition from the contralesional hemisphere and encouraging ipsilesional activation. The objective was to evaluate the efficacy of combined rTMS+BCI, compared to sham rTMS+BCI, on motor recovery after stroke in subjects with lasting motor paresis. Approach. Three stroke subjects approximately one year post-stroke participated in three weeks of combined rTMS (real or sham) and BCI, followed by three weeks of BCI alone. Behavioral and electrophysiological differences were evaluated at baseline, after three weeks, and after six weeks of treatment. Main Results. Motor improvements were observed in both real rTMS+BCI and sham groups, but only the former showed significant alterations in inter-hemispheric inhibition in the desired direction and increased relative ipsilesional cortical activation from fMRI. In addition, significant improvements in BCI performance over time and adequate control of the virtual reality BCI paradigm were observed only in the former group. Significance. When combined, the results highlight the feasibility and efficacy of combined rTMS+BCI for motor recovery, demonstrated by increased ipsilesional motor activity and improvements in behavioral function for the real rTMS+BCI condition in particular. Our findings also demonstrate the utility of BCI training alone, as demonstrated by behavioral improvements for the sham rTMS+BCI condition. This study is the first to evaluate combined rTMS and BCI training for motor rehabilitation and provides a foundation for continued work to evaluate the potential of both rTMS and virtual reality BCI training for motor recovery after stroke.

Abstract

Background

Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types.

Methods

We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. PROSPERO ID: CRD42016042055.

Results

We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events.

Conclusion

Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.

tDCS is relatively inexpensive, easy to administer and portable, hence constituting an ideal adjuvant therapy during stroke rehabilitation. It works by applying a weak and constant direct current to the brain and has the ability to either enhance or suppress cortical excitability, with effect lasting up to several hours after the stimulation [7, 8, 9]. Hypothetically, this technique makes tDCS a potentially useful tool to modulate neuronal inhibitory and excitatory networks of the affected and the non-affected hemisphere post stroke to enhance, for example, upper limb motor recovery [10, 11]. Three different stimulation types can be distinguished.

In anodal stimulation, the anodal electrode (+) usually is placed over the lesioned brain area and the reference electrode over the contralateral orbit [12]. This leads to subthreshold depolarization, hence promoting neural excitation [3].

In cathodal stimulation, the cathode (−) usually is placed over the non-lesioned brain area and the reference electrode over the contralateral orbit [12], leading to subthreshold polarization and hence inhibiting neural activity [3].

However, the literature does not provide clear guidelines, not only regarding the tDCS type, but also regarding the electrode configuration [14], the amount of current applied and the duration of tDCS, or the question if tDCS should be applied as a standalone therapy or in combination with other treatments, like robot-assisted therapy [15].

Rationale

There is so far conflicting evidence from systematic reviews of randomised controlled trials on the effectiveness of different tDCS approaches after stroke. For example, over the past two decades more than 30 randomised clinical trials have investigated the effects of different tDCS stimulation techniques for stroke, and there are 55 ongoing trials [16]. However, the resulting network of evidence from randomised controlled trials (RCTs) investigating different types of tDCS (i.e., anodal, cathodal or dual) as well as their comparators like sham tDCS, physical rehabilitation or pharmacological agents has not yet been analyzed in a systematic review so far.

A network meta-analysis (NMA), also known as multiple treatment comparison meta-analysis or mixed treatment comparison analysis, allows for a quantitative synthesis of the evidence network. This is made possible by combining direct evidence from head-to-head comparisons of three or more interventions within randomised trials with indirect evidence across randomised trials on the basis of a common comparator [17, 18, 19, 20]. Network meta-analysis has many advantages over traditional pairwise meta-analysis, such as visualizing and facilitating the interpretation of the wider picture of the evidence and improving understanding of the relative merits of these different types of neuromodulation when compared to sham tDCS and/or another comparator such as exercise therapy and/or pharmacological agents [21, 22]. By borrowing strength from indirect evidence to gain certainty about all treatment comparisons, network meta-analysis allows comparative effects that have not been investigated directly in randomised clinical trials to be estimated and ranked [22, 23].

Objective

The aim of our systematic review with NMA was to give an overview of the evidence network of randomised controlled trials of tDCS (anodal, cathodal, or dual) for improving capacity in activities of daily living (ADL) and upper limb function after stroke, as well as its safety, and to estimate and rank the relative effectiveness of the different stimulation types, while taking into account potentially important treatment effect modifiers.

The Oxford dictionary defines the term priming as “a substance that prepares something for use or action.” In this special issue, we define motor priming as a technique, experience, or activity targeting the motor cortex resulting in subsequent changes in motor behavior. Inadequate functional recovery after neural damage is a persisting burden for many, and this insufficiency highlights the need for new neurorehabilitation paradigms that facilitate the capacity of the brain to learn and recover. The concept of motor priming has gained importance in the last decade. Numerous motor priming paradigms have emerged to demonstrate success to improve functional recovery after injury. Some of the successful priming paradigms that have shown to alter motor behavior and are easily implementable in clinical practice include non-invasive brain stimulation, movement priming, motor imagery, and sensory priming. The full clinical impact of these priming paradigms has not yet been realized due to limited evidence regarding neural mechanisms, safety and effectiveness, dosage, individualization of parameters, identification of the appropriate therapies that need to be provided in combination with the priming technique, and the vital time window to maximize the effectiveness of priming. In this special issue, four manuscripts address critical questions that will enhance our understanding of motor priming paradigms and attempt to bridge the gap between neurophysiology and clinical implementation.

In their study, “Non-Invasive Brain Stimulation to Enhance Upper Limb Motor Practice Poststroke: A Model for Selection of Cortical Site,” Harris-Love and Harrington elegantly address the extremely important issue of individualizing brain stimulation for upper limb stroke recovery. Many brain stimulation techniques show high interindividual variability and low reliability as the “one-size-for-all” does not fit the vast heterogeneity in recovery observed in stroke survivors. In this article, the authors propose a novel framework that personalizes the application of non-invasive brain stimulation based on understanding of the structural anatomy, neural connectivity, and task attributes. They further provide experimental support for this idea with data from severely impaired stroke survivors that validate the proposed framework.

The issue of heterogeneity poststroke is also addressed by Lefebvre and Liew in “Anatomical Parameters of tDCS to modulate the motor system after stroke: A review.” These authors discuss the variability in research using tDCS for the poststroke population. According to the authors, the most likely sources of variability include the heterogeneity of poststroke populations and the experimental paradigms. Individually based variability of results could be related to various factors including: (1) molecular factors such as baseline measures of GABA, levels of dopamine receptor activity, and propensity of brain-derived neurotropic factor expression; (2) time poststroke, (3) lesion location; (4) type of stroke; and (5) level of poststroke motor impairment. Variability related to experimental paradigms include the timing of the stimulation (pre- or post-training), the experimental task, and whether the protocol emphasizes motor performance (a temporary change in motor ability) or motor learning based (more permanent change in motor ability). Finally, the numerous possibilities of electrode placement, neural targets, and the different setups (monocephalic versus bi-hemispheric) add further complexity. For future work with the poststroke population, the authors suggest that tDCS experimental paradigms explore individualized neural targets determined by neuronavigation.

In another exciting study in this issue, Estes et al. tackle the timely topic of spinal reflex excitability modulated by motor priming in individuals with spinal cord injury. The authors choose to test four non-pharmacological interventions: stretching, continuous passive motion, transcranial direct current stimulation, and transcutaneous spinal cord stimulation to reduce spasticity. Three out of four techniques were associated with reduction in spasticity immediately after treatment, to an extent comparable to pharmacological approaches. These priming approaches provide a low-cost and low-risk alternative to anti-spasticity medications.

In another clinical study in individuals with spinal cord injury, Gomes-Osman et al. examined effects of two different approaches to priming. Participants were randomized to either peripheral nerve stimulation (PNS) plus functional task practice, PNS alone, or conventional exercise therapy. The findings were unexpected. There was no change in somatosensory function or power grip strength in any of the groups. Interestingly, all of the interventions produced changes in precision grip of the weaker hand following training. However, only PNS plus functional task practice improved precision grip in both hands. The authors found that baseline corticospinal excitability were significantly correlated to changes in precision grip strength of the weaker hand. The lack of change in grip strength in any of the groups was surprising. Previous evidence suggests, however, that the corticomotor system is more strongly activated during precision grip as compared to power grip, and the authors suggest that interventions targeting the corticomotor system (i.e., various priming methods) may more strongly effect precision grip.

Overall, this special issue brings together an array of original research articles and reviews that further enhance our understanding of motor priming for motor recovery with an emphasis on neural mechanisms and clinical implementation. We hope that the studies presented encourage future studies on motor priming paradigms to optimize the potential for functional recovery in the neurologically disadvantaged population, and further our understanding of neuroplasticity after injury.

Author Contributions

SM and MS have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

SM is supported by funding from the National Institutes of Health (R01HD075777).

Abstract

The present review collects the most relevant empirical evidence available in the literature until date regarding the effects of transcranial direct current stimulation (tDCS) on the human motor function. tDCS in a non-invasive neurostimulation technique that delivers a weak current through the brain scalp altering the cortical excitability on the target brain area. The electrical current modulates the resting membrane potential of a variety of neuronal population (as pyramidal and gabaergic neurons); raising or dropping the firing rate up or down, depending on the nature of the electrode and the applied intensity. These local changes additionally have shown long-lasting effects, evidenced by its promotion of the brain-derived neurotrophic factor. Due to its easy and safe application and its neuromodulatory effects, tDCS has attracted a big attention in the motor neurorehabilitation field among the last years. Therefore, the present manuscript updates the knowledge available about the main concept of tDCS, its practical use, safety considerations, and its underlying mechanisms of action. Moreover, we will focus on the empirical data obtained by studies regarding the application of tDCS on the motor function of healthy and clinical population, comprising motor deficiencies of a variety of pathologies as Parkinson’s disease, stroke, multiple sclerosis and cerebral palsy, among others. Finally, we will discuss the main current issues and future directions of tDCS as a motor neurorehabilitation tool.

Background

The central nervous system (CNS) works thanks to the communication between more than 100,000 millions of neurons, whose activity and networking is modulated by chemical and electrical processes [1]. Across history, humans have been trying to alter the electrical brain processes to enhance human’s brain function, for the treatment of psychopathologies and for a better understanding of the brain physiology. For example, in the antiquity, modulation of the electrical processes of the brain started with the use of electrical impulses of torpedo fishes applied directly on the CNS, for therapeutic purposes [2]. In 1746, Musschenbroek (1692–1761) used Leyde jars and electrostatic devices to treat neuralgia, contractures and paralysis. The discovery of biometallic electricity and the invention of the voltaic battery augmented the interest in the therapeutic effects of galvanism. Afterwards, Duchenne de Boulogne (1806–1875) upgraded the electrotherapy with volta and magnetofaradaic apparatuses. Fortunately, in the past Century, the technological advances and its integration in health sciences have let us go from uncontrolled and unsafe interventions with side effects to well-controlled, more effective and safe stimulation devices [3].

Currently, the most used stimulation devices can be divided into invasive techniques, such as deep brain stimulation (DBS), and non-invasive brain stimulation (NiBS) techniques, whose most representative methods are transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) [4].

Although results are variable [5], DBS has reported positive results over the motor function, especially on the motor symptoms of Parkinson’s disease. However, DBS is a technique that needs the implantation of the electrodes on the stimulated area, which is associated with the typical risk derived from surgery, as infections. Therefore, there is an increasing tendence on the search for non-invasive brain stimulation techniques, which can modulate the motor function avoiding those risks.

Hence, NiBS are characterized for its easy and safe use and relatively cheap price, demonstrating also successful results in the treatment of neurological and psychiatric alterations [4]. In the last decades, TMS has been the most researched and developed neuromodulation technique. TMS generates fast changes in the magnetic field delivering electrical currents through the brain, allowing the specific modulation of the cortical excitability through the initiation of action potentials [6]. Multiple studies have already shown its efficacy and safe use for the treatment of multiple pathologies [7], serving also as a useful tool for the functional location of brain areas, especially regarding the motor cortex [8, 9]. However, TMS requires the participation of the participant, and due to its functioning, it is difficult to perform a sham condition, which is highly desirable especially in the research field. In addition, TMS produces in most of the cases undesirable side-effects, as headache [10].

Therefore, the tDCS technique is attracting a strong interest in the neuroscience research field. tDCS has supposed a revolution in the last 15 years of research, solving most of the disadvantages of TMS [10]. tDCS is a neuromodulation tool consisting on a battery connected to two electrodes, the anode and cathode, which are placed directly over the brain scalp and over extracephalic regions. The current flows between both electrodes and induces the depolarization or hyperpolarization of the membrane of the underlying neurons, which depends of the anodal or cathodal nature of the electrode [11], altering the neuronal excitability resulting in the modification of the brain activity [12]. This device is completely portable, as it is provided by built-in rechargeable battery with duration of approximately 6 h stimulation time at 1 mA (0.5–1.5 W of power consumption), and needs approximately 7 h for complete recharging. In addition, including battery, it has a weight of 0.8 kg. Its portability is one of the biggest advantages of tDCS in the context of NiBS. Therefore, tDCS can be considered as a suitable complementary technique on motor rehabilitation therapy, allowing its application in different contexes, during the motor training and even combined with aerobic exercise [13, 14].

This non-invasive brain manipulation has opened the doors for a variety of potential treatments for the major neurological and psychiatry diseases [15], as depression [16], schizophrenia [17], Obsessive–Compulsive disorder [18] and addictions [19], among others.

However, motor functions are the major target for clinical and non-clinical studies regarding tDCS, serving mainly as a potential tool in post-stroke rehabilitation [20], but also in pathologies like Parkinson’s disease [21]. In addition, numerous studies have shown that tDCS produces changes in the brain plasticity processes, generating long-lasting effects that enhances even further its applicability in the neurorehabilitation field [22, 23].

The purpose of this review is to assess the current and future stage of tDCS regarding its use on the human motor function, identifying the empirical cues that point out its benefits as well as its potential limitation, providing a comprehensive framework for designing future research in the field of brain stimulation with tDCS and human motor rehabilitation. The present review is divided in four parts. The first part is based on a detailed definition on what we know about tDCS, the protocols of montage and parameters of stimulation, comprising the mechanisms of action of tDCS, what differs tDCS from other non-invasive neuromodulation techniques, and the main need to-know safety standards. Given the conciseness of this first part, we will present the recent studies focusing exclusively on the empirical data obtained from the use of tDCS in the human motor function, regarding, in the second part, healthy humans; in the third part, its clinical application on deteriorated human motor functions across different pathologies as Parkinson disease, stroke and cerebral palsy. Finally, in the fourth part of this review, we will discuss the main current issues of tDCS applied on the human motor function.[…]

Each year, Americans spend billions of dollars on antidepressants. But studies show they can be ineffective in up to 40 percent of all patients.

Bob Holmes was one of them.

“They tried to adjust my medication, but the medication had side effects that weren’t desirable,” Holmes said.

Holmes is among the 16 million people in the U.S. who suffer major depressive episodes each year — a number that has increased 18 percent over the last decade. For that reason, some doctors at UCLA are taking a different approach.

“We are used to thinking of the brain as a chemical organ, but it’s also an electrical organ,” said Dr. Andrew Leuchter of UCLA Health.

“The idea that by using non-chemical means, we can change the brain and how it functions,” said Dr. Ian Cook of UCLA Health.

It is called transcranial magnetic stimulation, or TMS. It is currently approved by the Food and Drug Administration only to treat depression, but doctors say it may prove helpful in a wide range of conditions by rewiring a network of signals in the brain.

“What TMS is doing is changing how that network functions, really rebooting the network to improve symptoms of mood, anxiety and chronic pain,” Leuchter said.

That may be why patients treated for depression also say it helps relieve their pain, raising provocative questions about whether TMS could one day become a viable alternative to opioids.

“This is a really transformative kind of therapy,” Cook said.

But for now, it has made a dramatic difference in Holmes’ depression.

“It provided that kind of jolt to get my brain to start work again normally,” he said.

Reportedly, TMS can feel a bit uncomfortable at first — but many patients quickly get used to it. They report substantial relief from their symptoms of depression within a few weeks.

Even though the NeuroStar system has been approved for depression since 2008, it is only recently that doctors have realized its effectiveness for everything from post-traumatic stress disorder to obsessive-compulsive disorder.

Abstract

Background

Recovery of handgrip is critical after stroke since it is positively related to upper limb function. To boost motor recovery, transcranial direct current stimulation (tDCS) is a promising, non-invasive brain stimulation technique for the rehabilitation of persons with stroke. When applied over the primary motor cortex (M1), tDCS has been shown to modulate neural processes involved in motor learning. However, no studies have looked at the impact of tDCS on the learning of a grip task in both stroke and healthy individuals.

Objective

To assess the use of tDCS over multiple days to promote motor learning of a grip task using a learning paradigm involving a speed-accuracy tradeoff in healthy individuals.

Methods

In a double-blinded experiment, 30 right-handed subjects (mean age: 22.1 ± 3.3 years) participated in the study and were randomly assigned to an anodal (n = 15) or sham (n = 15) stimulation group. First, subjects performed the grip task with their dominant hand while following the pace of a metronome. Afterwards, subjects trained on the task, at their own pace, over 5 consecutive days while receiving sham or anodal tDCS over M1. After training, subjects performed de novo the metronome-assisted task. The change in performance between the pre and post metronome-assisted task was used to assess the impact of the grip task and tDCS on learning.

Conclusions

Anodal tDCS is effective in promoting grip motor learning in healthy individuals. Further studies are warranted to test its potential use for the rehabilitation of fine motor skills in stroke patients.

Results

There was no significant effect of tDCS on PASSMA→M1 induced plasticity in the repeated-measures ANOVA. However, post-hoc within-subject contrasts revealed a significant tDCS with PASSMA→M1 interaction. This was explained by PA-tDCS and AP-tDCS modifying the PASSMA→M1 effect into the same direction in 13/15 subjects (87%, p = 0.004 for deviation from equality). Sizes of the PA-tDCS and AP-tDCS effects were correlated (rs = 0.53, p = 0.044). A control experiment demonstrated that PA-tDCS and AP-tDCS alone (without PASSMA→M1) had no effect on MEP amplitude.

Conclusions

Data point to unidirectional tDCS effects on PASSMA→M1 induced plasticity irrespective of tDCS polarity, in contrast to our hypothesis. We propose that radial symmetry of cortical columns, gyral geometry of motor cortex, and cooperativity of plasticity induction can explain the findings.

John O’Reardon, MD is a leading expert on the use of transcranial magnetic stimulation (TMS) in the treatment of mental disorder. In this 30-minute interview, he gives mental health clinicians essential information about this important treatment option.

He answers many practical questions that occurred to me about TMS. Which patients are ideal to be referred for TMS? How can we find out if the patient’s insurance will pay for it? How exactly is TMS delivered? Why is it important for TMS to be delivered by an expert? What should be done if the patient does respond to TMS? What should be done if the patient does not respond to the TMS? He briefly answers all these and many more.

Introduction: Recent studies suggest that repeated transcranial magnetic stimulation (TMS) improves functional movement disorders (FMDs), but the underlying mechanisms are unclear. The objective was to determine whether the beneficial action of TMS in patients with FMDs is due to cortical neuromodulation or rather to a cognitive-behavioral effect.

Method: Consecutive patients with FMDs underwent repeated low-frequency (0.25 Hz) magnetic stimulation over the cortex contralateral to the symptoms or over the spinal roots [root magnetic stimulation (RMS)] homolateral to the symptoms. The patients were randomized into two groups: group 1 received RMS on day 1 and TMS on day 2, while group 2 received the same treatments in reverse order. We blindly assessed the severity of movement disorders before and after each stimulation session.

Results: We studied 33 patients with FMDs (dystonia, tremor, myoclonus, Parkinsonism, or stereotypies). The median symptom duration was 2.9 years. The magnetic stimulation sessions led to a significant improvement (>50%) in 22 patients (66%). We found no difference between TMS and RMS.

Conclusion: We suggest that the therapeutic benefit of TMS in patients with FMDs is due more to a cognitive-behavioral effect than to cortical neuromodulation.

Introduction

Individuals with functional movement disorders (FMDs) account for 3–20% of all patients seen in movement-disorder clinics (1–3). There is no consensus treatment for FMDs (4–6). These movement disorders are not due to irreversible brain damage but their outcome is nonetheless poor: symptoms are persistent or worse after 1.5–7 years of follow-up in between 44 and 90% of patients (6, 7). FMDs generate major healthcare costs, as well as indirect costs due to unemployment and disability (8).

Recent studies suggest a beneficial effect of repeated supraliminal low-frequency transcranial magnetic stimulation (TMS) (i.e., TMS ≤ 1 Hz) on functional motor symptoms (9–14) [Ref. (15) for a review]. Among these studies, only one included a blinded assessment (11), and only one included a control group (sham treatment) (9). Focusing on FMDs more specifically, two studies showed a beneficial effect of supraliminal low-frequency TMS, with a mean improvement rate of 67% (11) and 97% (13). It is unclear whether the therapeutic benefit is due to cortical neuromodulation, i.e., to changes in cortical excitability and in connectivity between brain areas (15, 16). The alternative hypothesis is a cognitive-behavioral effect, a therapeutic effect that is linked to suggestion and/or motor relearning.

To address this issue, we blindly compared the therapeutic effect of repeated TMS and repeated root magnetic stimulation (RMS) in patients with FMDs. RMS was chosen as the control treatment to mimic TMS-induced movement without directly stimulating the cortex.

This book is the first comprehensive work summarizing the advances that have been made in the neurosurgical use of navigated transcranial magnetic stimulation (nTMS) over the past ten years. Having increasingly gained acceptance as a presurgical mapping modality in neurosurgery, today it is widely used for preoperative mapping of cortical motor and language function, risk stratification and improving the accuracy of subcortical fiber bundle visualization.

This unique work will provide neurosurgeons and neuroscientists who are starting their nTMS program essential and detailed information on the technique and protocols, as well as the current clinical evidence on and limitations of the various applications of nTMS. At the same time, more experienced nTMS users looking for deeper insights into nTMS mapping and treatment in neurosurgery will find clearly structured, accessible information. The book was prepared by an international mix of authors, each of which was chosen for their status as a respected expert on the respective subtopic, as evinced by their landmark publications on nTMS.